chr9-6240084-T-C

Variant names:

• chr9-6240084-T-C
• rs7025417
• NM_033439.4:c.-11-1600T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033439.4(IL33):​c.-11-1600T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,130 control chromosomes in the GnomAD database, including 4,023 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4023 hom., cov: 32)
• Consequence: IL33 NM_033439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• Publications: 31 publications found

Genes affected

IL33 (HGNC:16028): (interleukin 33) The protein encoded by this gene is a cytokine that binds to the IL1RL1/ST2 receptor. The encoded protein is involved in the maturation of Th2 cells and the activation of mast cells, basophils, eosinophils and natural killer cells. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2015]

ENSG00000294323 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IL33	NM_033439.4	c.-11-1600T>C		intron_variant	Intron 1 of 7	ENST00000682010.1	NP_254274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IL33	ENST00000682010.1	c.-11-1600T>C		intron_variant	Intron 1 of 7		NM_033439.4	ENSP00000507310.1
IL33	ENST00000417746.6	c.-11-1600T>C		intron_variant	Intron 1 of 4	2		ENSP00000394039.2
ENSG00000294323	ENST00000722750.1	n.187-11789A>G		intron_variant	Intron 2 of 3
ENSG00000294323	ENST00000722751.1	n.231+3696A>G		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33624 AN: 152010 Hom.: 4005 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33647 AN: 152130 Hom.: 4023 Cov.: 32 AF XY: 0.220 AC XY: 16370 AN XY: 74358

African (AFR) AF: 0.206 AC: 8536 AN: 41496

American (AMR) AF: 0.167 AC: 2559 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2443 AN: 5156

South Asian (SAS) AF: 0.240 AC: 1157 AN: 4822

European-Finnish (FIN) AF: 0.228 AC: 2417 AN: 10582

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15076 AN: 68004

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.221 Hom.: 9568

Bravo AF: 0.217

Asia WGS AF: 0.383 AC: 1331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7025417; hg19: chr9-6240084;